LncRNA HCG27 Promotes Glucose Uptake Ability of HUVECs by MiR-378a-3p/MAPK1 Pathway

Objective:Gestational diabetes mellitus(GDM)is the most common metabolic disorder during pregnancy.LncRNA HLA complex group 27(HCG27)plays a crucial role in various metabolic diseases.However,the relationship between lncRNA HCG27 and GDM is not clear.This study aimed to verify a competing endogenous RNA(ceRNA)interaction regulation axis of miR-378a-3p/mitogen-activated protein kinase 1(MAPK1)regulated by HCG27 in GDM.Methods:LncRNA HCG27 and miR-378a-3p were detected by RT-qPCR.The expression of MAPK1 in umbilical vein endothelial cells(HUVECs)was detected by RT-qPCR and that in the placenta by Western blotting.To explore the relationship among lncRNA HCG27,miR-378a-3p,MAPK1 and the glucose uptake ability of HUVECs,vector HCG27,si-HCG27,miR-378a-3p mimic and inhibitor were transfected to achieve overexpression and inhibition of HCG27 or miR-378a-3p.The interaction between miR-378a-3p and lncRNA HCG27 or MAPK1 was confirmed by the dual-luciferase reporter assay.Besides,glucose consumption by HUVECs was detected by the glucose assay kit.Results:HCG27 expression was significantly decreased in both the placenta and primary umbilical vein endothelial cells,while the expression of miR-378a-3p was significantly increased in GDM tissues,and the expression of MAPK1 was decreased in GDM tissues.This ceRNA interaction regulation axiswas proved to affect the glucose uptake function of HUVECs.The transfection of si-HCG27 could significantly reduce the expression of the MAPK1 protein.If the MAPK1 overexpression plasmid was transfected simultaneously with si-HCG27 transfection,the reduced glucose uptake in HUVECs resulting from the decrease in lncRNA HCG27 was reversed.MiR-378a-3p mimic can significantly reduce the mRNA expression of MAPK1 in HUVECs,whereas miR-378a-3p inhibitor can significantly increase the mRNA expression of MAPK1.The inhibition of miR-378a-3p could restore the decreased glucose uptake of HUVECs treated with si-HCG27.Besides,overexpression of lncRNA HCG27 could restore the glucose uptake ability of the palmitic acid-induced insulin resistance model of HUVECs to normal.Conclusion:LncRNA HCG27 promotes glucose uptake of HUVECs by miR-378a-3p/MAPK1 pathway,which may provide potential therapeutic targets for GDM.Besides,the fetal umbilical cord blood and umbilical vein endothelial cells collected from pregnant women with GDM after delivery could be used to detect the presence of adverse molecular markers of metabolic memory,so as to provide guidance for predicting the risk of cardiovascular diseases and health screening of offspring.

Silencing of DsbA-L gene impairs the PPARγagonist function of improving insulin resistance in a high-glucose cell model

Disulfide-bond A oxidoreductase-like protein(DsbA-L)is a molecular chaperone involved in the multimeri-zation of adiponectin.Recent studies have found that DsbA-L is related to metabolic diseases including gestational diabetes mellitus(GDM),and can be regulated by peroxisome proliferator-activated receptorγ(PPARγ)agonists;the specific mechanism,however,is uncertain.Furthermore,the relationship between DsbA-L and the novel adipokine chemerin is also unclear.This article aims to investigate the role of DsbA-L in the improvement of insulin resistance by PPARγagonists in trophoblast cells cultured by the high-glucose simulation of GDM placenta.Immunohistochemistry and western blot were used to detect differences between GDM patients and normal pregnant women in DsbA-L expression in the adipose tissue.The western blot technique was performed to verify the relationship between PPARγagonists and DsbA-L,and to explore changes in key molecules of the insulin signaling pathway,as well as the effect of chemerin on DsbA-L.Results showed that DsbA-L was significantly downregulated in the adipose tissue of GDM patients.Both PPARγagonists and chemerin could upregulate the level of DsbA-L.Silencing DsbA-L affected the function of rosiglitazone to promote the phosphatidylinositol 3-kinase(PI3K)-protein kinase B(PKB)/AKT pathway.Therefore,it is plausible to speculate that DsbA-L is essential in the environment of PPARγagonists for raising insulin sensitivity.Overall,we further clarified the mechanism by which PPARγagonists improve insulin resistance.

Genetic Variants of Potassium Voltage-gated Channel Subfamily J Member 11 in Gestational Diabetes Mellitus:A Case-control Study

Objective::To investigate the association of rs5210 in potassium voltage-gated channel subfamily J member 11(KCNJ11)with gestational diabetes mellitus(GDM).Methods::Six hundred and thirty-two uncorrelated pregnancy females were recruited in Tongji hospital from October 2017 to June 2018,in which 241 pregnant women were identified as GDM,and 391 were non-GDM.All the pregnant women recruited in this study their peripheral venous blood of 5 mL were withdrawn,and DNA in the blood was extracted.rs5210 in KCNJ11 were genotyped using TaqMan Assays and genotype models were analyzed using logistic regression analyses.Results::After adjusting age and body mass index,the variant genotypes of rs5210 in genotype models were as follows:P for dominant model was 0.945,(odd ratio:0.987,95%confidence intervals(CI):0.681-1.430);P for recessive model:0.556,(odd ratio:1.217,95%CI:0.633-2.343)and P for addictive model was 0.098(genotype AA vs.GG),(odds ratio:1.435,95%CI:0.936-2.201).Weight-gain during pregnancy and total cholesterol were significantly different in recessive model(P=0.015,P=0.022,respectively)of all participants.Conclusion::No significant association between gene susceptibility of rs5210 in KCNJ11 and GDM occurrence in Chinese pregnant women.But the variant of rs5210 was associated with weight-gain during pregnancy and total cholesterol blood levels.However,more cases are needed in genetic study to check its susceptibility with GDM occurrence in Chinese women.